The current use of photodynamic therapy (PDT) is founded on evidence from a series of well-designed clinical trials. Work in animal models clearly demonstrated the therapeutic potential of PDT with verteporfin for choroidal neovascularization (CNV) (see Chapter 9). These preclinical studies proved that verteporfin PDT could occlude experimental laser-induced CNV, confirmed by cessation of angiographic leakage on fluorescein angiography and thrombosis of vessels on histologic examination (1–3). Treatment parameters for maximum selectivity were refined by manipulating drug and light doses and the timing of light irradiation, resulting in minimal effect on the choroid and surrounding retina. Although damage was noted at the level of the choriocapillaris and retinal pigment epithelium (RPE), recovery of these structures was observed after both single and repeated PDT (4,5). The preclinical data provided the rationale for a clinical Phase I and II study to assess the safety of PDT and to determine the maximum tolerated dose of PDT using verteporfin for treatment of CNV. Based on encouraging results from these Phase I and II investigations, large Phase III trials followed, providing guidelines for the application of PDT in clinical practice today.